Characterizing advanced breast cancer heterogeneity and treatment resistance through serial biopsies and comprehensive analytics

Allen Li, Jamie M. Keck, Swapnil Parmar, Janice Patterson, Marilyne Labrie, Allison L. Creason, Brett Johnson, Molly Downey, George Thomas, Carol Beadling, Laura M. Heiser, Annette Kolodzie, Alexander Guimaraes, Christopher L. Corless, Joe Gray, Gordon Mills, Raymond C. Bergan, Zahi I. Mitri

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Molecular heterogeneity in metastatic breast cancer presents multiple clinical challenges in accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess heterogeneity that exists among multiple metastatic lesions throughout the treatment course. We developed a precision oncology platform that combines serial biopsies, multi-omic analysis, longitudinal patient monitoring, and molecular tumor boards, with the goal of improving cancer management through enhanced understanding of the entire cancer ecosystem within each patient. We describe this integrative approach using comprehensive analytics generated from serial-biopsied lesions in a metastatic breast cancer patient. The serial biopsies identified remarkable heterogeneity among metastatic lesions that presented clinically as discordance in receptor status and genomic alterations with mixed treatment response. Based on our study, we highlight clinical scenarios, such as rapid progression or mixed response, that indicate consideration for repeat biopsies to evaluate intermetastatic heterogeneity (IMH), with the objective of refining targeted therapy. We present a framework for understanding the clinical significance of heterogeneity in breast cancer between metastatic lesions utilizing multi-omic analyses of serial biopsies and its implication for effective personalized treatment.

Original languageEnglish (US)
Article number28
Journalnpj Precision Oncology
Volume5
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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